Healthcare inequities in Latin America outweigh the benefits of pediatric regimens in adult acute lymphoblastic leukemia

Abstract

Abstract Background: In Latin America, leukemia care is delivered through two distinct healthcare systems: a public health system, which serves approximately 70% of the population, and a private system. Acute lymphoblastic leukemia (ALL) is a neoplasm that requires complex, intensive, multi-agent chemotherapy regimens, leading to profound immunosuppression and a high demand for supportive care. In public institutions, most patients are treated according to institutional pediatric-inspired protocols, whereas in the private sector, a smaller proportion receives similarly adapted regimens. Currently, there is no comprehensive regional database for acute leukemia in Latin America that allows for the assessment of outcome disparities related to healthcare access or biological factors. In this study, we sought to analyze outcomes in a large, multicenter cohort that includes both public and private institutions, with the goal of identifying key factors associated with survival in adult patients with ALL. Methods: This is a retrospective multi-site cohort study encompassing patients from 15 years and above with newly diagnosed ALL between 2010 and 2024 from 7 centers from Brazil and 13 centers from Chile. Results: A total of 578 patients were included, mostly from Brazil (65.7%). Median age was 37.5 years (range, 15-87) and 52.6% were male. Most cases were B-lineage (82%), and 28% were Ph+. Leukocytosis (≥30 for B or ≥100 for T-lineage) was registered in 21.4% and CNS disease in 16.8%. In this cohort, 252 patients (43.6%) were treated in private centers, while remaining cases were treated in the public system. In the Ph-negative younger subset (≤60 years), pediatric-inspired protocols were the most common regimens in public centers (82.1%), while Hyper-CVAD was the most frequent in private (54.5%). Inversely, for elderly patients (>60y), pediatric-inspired regimens were more adapted for this population in the private (64.7%) than in the public setting (30.8%) (p=0.001). No statistical differences in baseline disease characteristics were observed between patients from public and private scenarios. Regarding Ph+ cases, more cases from private setting received dasatinib instead imatinib frontline (73.1 vs. 28.1%, p<0.001), while only 8 patients received upfront ponatinib (all private). Overall, the induction death rate was 15.7 and 2.8% in the public and private scenarios, respectively. Fourteen patients from the private cohort received blinatumomab in the relapsed/refractory setting. The rate of allogeneic stem-cell transplant (HCT) was greater in private centers than in public ones (59.1 vs. 33.1%, p<0.001), mostly in first complete remission (86.2 vs. 82.7%). Baseline transplant characteristics did not differ between the two scenarios. With a median follow-up of 43 months, 4-year overall survival (OS) were 34.9 and 51.6% in the public and private centers, respectively (p<0.001), while 4-year event-free survival were 32.9 and 45.2%. For younger Ph-negative pts (n=254), age (HR 1.03, 95% CI 1.004-1.05, p<0.001) and extramedullary disease (HR 2.971, 95% CI 1.574-5.605, p<0.001) were independently associated with OS. No benefit of frontline pediatric regimen was observed in this population (HR 1.08, 95% CI 0.776-1.49, p=0.66), neither for allogeneic HCT in CR1 (time-dependent variable) (HR 1.3, 95% CI 0.839-2.01, p=0.24) in the MVA. There was no statistical benefit for pediatric regimens within the private (p=0.075), only for public setting (HR 0.4671, 95% CI 0.24-0.91, p=0.025). For Ph+ patients, there was benefit in favor of dasatinib upfront (HR 0.544, 95% CI 0.338-0.874, p=0.012). Treatment in a private center (HR 0.53, 95% CI 0.42-0.68, p<0.001) was independently associated with OS globally and in all subgroups (B vs. T, Ph+, elderly), even when adjusted for age, CNS disease, and HCT in CR1 in the MVA. Conclusions: The impact of socioeconomic factors on outcomes in adult ALL appears to be particularly significant in Latin America. Beyond financial disparities, improved infrastructure, access to blinatumomab and later line TKIs, and the availability of HCT have a direct effect on patient survival. In contrast, public centers – despite treating many patients with pediatric-inspired protocols – continue to face limitations that substantially contribute to poorer outcomes. Our findings also suggest that, with availability of new agents and HCT, pediatric protocols might not benefit all young ALL patients.